Studies will examine mechanisms for increased vulnerability to ischemia in the pressure-loaded hypertrophied left ventricle, and determine whether development of myocardial dysfunction can be attributed to abnormal perfusion. Left ventricular hypertrophy will be produced by ascending aortic banding or by creating valvular aortic stenosis in young dogs; hypertrophy occurs as the pressure overload increases during normal growth in the presence of fixed aortic narrowing. At the time of study, the transmural distribution of blood flow is measured with microspheres while subendocardial and subepicardial contractile function are examined with ultrasonic microcrystals. Since myocardial creatine phosphate, inorganic phosphate and ATP are sensitive indicators of oxygen availability, these variables will be measured in 5 transmural layers across the left ventricular wall using 31P-NMR spectroscopy. An initial study will determine whether adrenergic activity during exercise acts to constrict subepicardial vessels, thereby enhancing subendocardial perfusion and contractile function. A second study will examine coronary pressure-flow relationships to assess the relative importance of vascular and extravascular factors in limiting blood flow in the hypertrophied heart. A third protocol will determine whether cardiac failure is associated with depletion of myocardial creatine phosphate or ATP, and accumulation of inorganic phosphate, to determine whether these may be clinically useful markers of myocardial dysfunction. A fourth study will determine whether increased extravascular forces resulting from subendocardial ischemia contribute to subendocardial underperfusion during tachycardia in the hypertrophied heart. A fifth protocol will determine whether inotropic stimulation with dobutamine results in further depletion of creatine phosphate in hypertrophied hearts, and whether this abnormality is reversed by hyperperfusion, indicating inadequate blood flow. A sixth study will determine whether subendocardial underperfusion during exercise in the hypertrophied left ventricle results in post-exercise stunning, which may contribute to the development of persistent dysfunction in the hypertrophied heart. A final study will determine whether post-exercise stunning is associated with disruption of the myocardial extracellular collagen matrix, which could allow dilatation of the dysfunctional hypertrophied heart. The results of these studies will be directly applicable to 31P-NMR spectroscopy in patients, and will assist in identifying abnormalities which may allow early identification of myocardial dysfunction in patients with left ventricular hypertrophy.